There is a continually expanding need to determine the presence of minute quantities of organic materials in aqueous solutions and to quantify their concentrations. Concentrations of interest range from about 10.sup.-4 to 10.sup.-12 M or even lower. Areas where the determinations are most significant include detecting the presence of drugs of abuse in physiological media, metering of therapeutic dosages of drugs, diagnosis of disease where the presence, absence or amount of a particular organic material is relevant to the diagnosis, and in assays for trace contaminants of food. Non-physiological areas of interest include investigations of water contamination, quality control, and the like. Despite major advances in the immunoassay field, the precise determination of low concentrations of organic compounds continue to present problems, and many important compounds still cannot be routinely detected or measured.
Sandwich immunoassays were developed to provide increased sensitivity. In these procedures, an antibody which selectively binds to an analyte is provided with a hapten label. A second antibody, which selectively binds with the hapten label, is provided. The second antibody is provided with a detector label, e.g. a radioactive element, fluorescent substituent, enzyme, or the like which can be used to quantify the amount of detector labeled conjugate. Applying hapten labels to antibodies presents a number of special problems. Antibody solubility is reduced when bound to previously used haptens. Since most assays are carried out in aqueous medium, this insolubility presents a limiting aspect of hapten labeling. Furthermore, many haptens reduce antibody activity when coupled to the antibody.